USE1 Inhibitors

Chemical inhibitors of USE1 can impede the protein's function by targeting various cellular mechanisms involved in vesicular transport. Alsterpaullone operates by inhibiting CDK5/p25 complex, a kinase which indirectly affects USE1's role in the neuronal signaling pathways that oversee vesicular transport through phosphorylation events. Similarly, Roscovitine targets cyclin-dependent kinases (CDKs) that regulate intracellular transport, thus indirectly affecting USE1's function. Gö6976 exerts its action by selectively inhibiting protein kinase C isoforms, which are involved in the regulation of intracellular trafficking, including vesicular fusion and transport processes that USE1 facilitates. Wortmannin's inhibitory effects on phosphoinositide 3-kinases disrupt vesicle formation, impairing USE1's role in this process.

Concurrently, agents that disrupt cytoskeletal components essential for vesicle movement also functionally inhibit USE1. Latrunculin A binds to actin monomers, preventing their polymerization, which is crucial for vesicle motility. Y-27632 inhibits Rho-associated protein kinase, affecting the actin cytoskeleton organization and, consequently, vesicle transport that USE1 is involved in. ML-7, by inhibiting myosin light chain kinase, impedes myosin activation for vesicle movement, thereby affecting USE1 function. Compounds like Nocodazole and Vinblastine disrupt microtubule dynamics, a critical component of the cellular scaffold that supports vesicular trafficking involving USE1, with nocodazole disassembling microtubules and vinblastine preventing their assembly. In contrast, Taxol stabilizes microtubules, which can also affect USE1's role by preventing the dynamic rearrangement of microtubules necessary for vesicular transport. Lastly, Brefeldin A and Thapsigargin target the organelle function and calcium homeostasis, respectively, with Brefeldin A disrupting the Golgi apparatus and Thapsigargin inhibiting the sarco/endoplasmic reticulum Ca2+-ATPase, both leading to conditions that impede USE1's role in vesicle fusion.